Open AccessDisrupted‐in‐schizophrenia 1 functional polymorphisms and D 2 /D 3 receptor availability: A [ 11 C]‐(+)‐PHNO imaging study
Author(s) -
Dahoun Tarik,
Nour Matthew M.,
Adams Rick A.,
Trossbach Svenja,
Lee Sang H.,
Patel Hamel,
Curtis Charles,
Korth Carsten,
Howes Oliver D.
Publication year - 2019
Publication title -
genes, brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 91
eISSN - 1601-183X
pISSN - 1601-1848
DOI - 10.1111/gbb.12596
Subject(s) - dopamine receptor d2 , disc1 , putamen , dopamine , schizophrenia (object oriented programming) , striatum , ventral striatum , antipsychotic , receptor , neuroscience , biology , genetics , psychology , psychiatry , gene
The disrupted‐in‐schizophrenia 1 (DISC1) protein has been implicated in a range of biological mechanisms underlying chronic mental disorders such as schizophrenia. Schizophrenia is associated with abnormal striatal dopamine signalling, and all antipsychotic drugs block striatal dopamine 2/3 receptors (D 2/3 Rs). Importantly, the DISC1 protein directly interacts and forms a protein complex with the dopamine D 2 receptor (D 2 R) that inhibits agonist‐induced D 2 R internalisation. Moreover, animal studies have found large striatal increases in the proportion of D 2 R receptors in a high affinity state (D 2 high R) in DISC1 rodent models. Here, we investigated the relationship between the three most common polymorphisms altering the amino‐acid sequence of the DISC1 protein (Ser704Cys (rs821616), Leu607Phe (rs6675281) and Arg264Gln (rs3738401)) and striatal D 2/3 R availability in 41 healthy human volunteers, using [ 11 C]‐(+)‐PHNO positron emission tomography. We found no association between DISC1 polymorphisms and D 2/3 R availability in the striatum and D 2 R availability in the caudate and putamen. Therefore, despite a direct interaction between DISC1 and the D 2 R, none of its main functional polymorphisms impact striatal D 2/3 R binding potential, suggesting DISC1 variants act through other mechanisms.